One of every 11 American women will develop mammary cancer (MC) during her life-time. While detection of localized MC can allow curative surgery, unfortunately, many patients are initially diagnosed with or eventually develop disseminated disease not curable by surgery alone. Patients with metastatic MC do respond to hormonal and/or chemotherapy, however, these responses are rarely curative. To develop more effective treatments for metastatic MC, new approaches are required. Recent animals have suggested such a new approach. This lead is based upon the observation that not all inbred strains of rats are equally susceptible to either spontaneous or chemical induction of MC. A large series of genetically inbred strains of female rats have been compared for their susceptibility to both dimethylbenzanthracene (DMBA) and N-methyl nitrourea (MNU) induced mammary carcinogenesis. The inbred Sprague-Dawley (NSD) and Osborne-Mendel (OM) strains are the most susceptible developing > 3 MC/rat and the inbred Copenhagen (Cop) the least susceptible developing 0 MC/rat. This differential susceptibility is due to intrinsic differences in the mammary epithelial cells themselves and not to differences in the host systemic environment. When inbred NSD or OM rats are crossbred to Cop animals, the resultant F1 hybrid females are resistant to the development of MC like their Cop parent. Further studies demonstrated that Mendelian inheritance of a single copy of a dominantly acting autosomal allele from the Cop genome is capable of suppressing the development of continuously growing mammary cancers following exposure of the host to DMBA or MNU. In addition, when Cop mammary epithelial cells are fused with established mammary cancer induced by DMBA treatment of an SD rat, the resulting somatic cell hybrids are non-tumorigenic. This suggests that a specific allele present within the Cop genome is able to actively suppress the tumorigenicity of DMBA induced MC. The specificity and generality of the ability of this Cop MC suppressor gene to actively suppress tumorigenicity when introducing into MC cells by means of somatic cell fusion will be treated. Attempts will be made to clone the c-DNA corresponding to this MC suppressor gene.